Antonio Pio Tortorelli

Is malnutrition still a risk factor of postoperative complications in gastric cancer surgery

OBJECTIVE & AIMS The present study aimed at retrospectively evaluating the incidence of mortality and major and minor postoperative complications in patients who underwent surgery for gastric cancer between 2000 and 2006 stratified according to the preoperative percentage weight loss, serum albumin levels and body mass index (BMI). METHODS One hundred and ninety-six patients affected by gastric cancer admitted to the Division of Digestive Surgery of the Catholic University of Rome between January 2000 and December 2006 were considered eligible and were included in the study. According to the weight loss, patients were divided into three groups: (1) 0-5%; (2) 5.1-10%; (3) >10%. On the basis of serum albumin levels, were divided into three groups: (1) <3.0 g/dl; (2) 3.0-3.4 g/dl; (3) >3.5 g/dl. According to BMI, were divided into four groups: (1) <18.5 kg/m(2); (2) 18.5-24.9 kg/m(2); (3) 25.0-29.9 kg/m(2); (4) >30.0 kg/m(2). Postoperative complications and mortality were reported. Complications were classified by objective criteria as major or minor, and as infectious or non-infectious. RESULTS The postoperative mortality was 0%. Major infectious complications occurred in 20 patients (10.2%), major non-infectious in 18 (9.2%), minor infectious in 21 (10.7%), whereas minor non-infectious complications were absent. The rate of major infectious, major non-infectious and minor infectious postoperative complications was similar in patients with absent or light weight loss (8.8%, 8.8%, 10.6%, respectively), mild weight loss (15.3%, 11.5%, 9.6%, respectively), or severe weight loss (6.4%, 6.4%, 12.9%, respectively). Similarly, the rate of postoperative complications did not differ between patients with serum albumin <3.0 g/dl (10.8%, 8.1%, 8.1%, respectively); between 3.0 and 3.4 (8.8%, 13.3%, 17.7%, respectively) or > or =3.5 g/dl (10.5%, 7.9%, 8,7%, respectively). According to BMI, the rate of postoperative complications was: 11.7%, 5.8%, and 5.8% for BMI <18.5 kg/m(2); 9.4%, 8.2%, and 11.7% for BMI between 18.5 and 24.9 kg/m(2); 10.7%, 10.7%, and 9.2% for BMI between 25 and 29.9 kg/m(2); 10.3%, 10.3% and 13.7% for BMI >30 kg/m(2). Then, we evaluated the postoperative morbidity only in patients who underwent total gastrectomy or distal subtotal gastrectomy associated with extended lymphadenectomy. In this group of patients, the rate of postoperative complications was comparable in patients with 0-5% (8.8%, 7.7%, 10%, respectively), 5.1-10% (14.6%, 9.7%, 9.7%, respectively), and >10% (7.1%, 7.1%, 14.3%, respectively) weight loss. Also stratifying the patients according to the serum albumin levels, the rate of postoperative complications did not differ significantly (serum albumin <3.0 g/dl: 14.8%, 11.1%, 14.8%, respectively; serum albumin between 3.0 and 3.4 g/dl: 6.2%, 12.5%, 15.6%, respectively; serum albumin > or =3.5 g/dl: 10.4%, 5.8%, 7.0%, respectively). According to BMI, the rate of postoperative complications was: 7.6%, 0%, and 7.6% for BMI <18.5 kg/m(2); 9.5%, 9.5%, and 11.1% for BMI between 18.5 and 24.9 kg/m(2); 12.5%, 8.3%, and 10.4% for BMI between 25 and 29.9 kg/m(2); 9.5%, 9.5% and 9.5% for BMI >30 kg/m(2). CONCLUSION The present study suggests that weight loss and hypoalbuminemia are not associated with an increased risk of mortality and morbidity in patients who underwent surgery for gastric cancer. This study may represent a stimulus for further studies aiming at evaluating the actual role of malnutrition in the development of postoperative complications in major abdominal surgery.

Cancer Cachexia: It’s Time for More Clinical Trials

Cancer cachexia (CC) is a multifactorial paraneoplastic syndrome characterized by anorexia, body weight loss, loss of adipose tissue and skeletal muscle, accounting for at least 20% of deaths in neoplastic patients. CC significantly impairs quality of life and response to anti-neoplastic therapies, increasing morbidity and mortality of cancer patients. Muscle wasting is the most important phenotypic feature of CC and the principal cause of function impairment, fatigue and respiratory complications, mainly related to a hyperactivation of muscle proteolytic pathways. Most current therapeutic strategies to counteract CC have proven to be only partially effective. In the last decade, the correction of anorexia, the inhibition of catabolic processes and the stimulation of anabolic pathways in muscle have been attempted pharmacologically with encouraging results in animal models and through preliminary clinical trials. However, data in the clinical setting are still scanty and non definitive. It is time to start prospective, randomized, controlled trials to evaluate which drugs are effective in counteracting the loss of lean of muscle mass and in improving nutritional status and quality of life in patients affected by cancer-related cachexia.

Skeletal muscle in cancer cachexia: the ideal target of drug therapy

Cancer cachexia is a debilitating and life-threatening syndrome that accounts for at least 20% of deaths in neoplastic patients. Cancer cachexia significantly impairs quality of life and response to anti-neoplastic therapies, increasing morbidity and mortality of cancer patients. The loss of lean body mass is the main characteristic of cancer cachexia and the principal cause of function impairment, fatigue and respiratory complications. It is the result of an imbalance between protein synthesis and protein degradation, the mechanisms underlying such alteration being multiple and partially known. Current therapy of cancer cachexia continues to be extremely poor. However, in the last decade, the attention has focused just on the skeletal muscle, as a potential target of therapy, with the aim to discover drugs capable to inhibit the catabolic processes and to stimulate the anabolic pathways. The skeletal muscle has been faced at different levels such as the mediators (cytokines and tumor-derived factors), the receptors (TNF-alpha and androgen receptors), the proteolytic pathways (calpains and ubiquitin-proteasome), the intracellullar signalling pathways (NF-kB, AP-1, FOXO, PKR), and the negative modulators of muscle growth/hypertrophy (myostatin, GSK3-beta). Most of the drugs that have been tested have shown to be effective, at least in experimental models of cancer cachexia. It remains to define their safety, tolerance and efficacy in humans through large, adequate, clinical trials. However, the impression is that there is a light at the back of the tunnel.

Retroperitoneal soft tissue sarcoma: prognostic factors and therapeutic approaches.

Aims and Background Retroperitoneal sarcomas are a rare group of malignant soft tissue tumors with a generally poor prognosis. The aim of the study was to assess clinical, pathological and treatment-related factors affecting prognosis in patients with retroperitoneal sarcomas. Methods and Study Design The hospital records of 73 patients who underwent surgical exploration at our unit for primary retroperitoneal sarcomas between 1984 and 2003 were reviewed. Factors influencing overall and disease-free survival were analyzed for all patients and for those who underwent complete surgical resection. Results The complete resectability rate was 69.8% (51/73). Operative mortality and morbidity rates were 2.7% and 21.9%, respectively. For patients who underwent complete resection, the 5-year survival rate was 58.3%, whereas it was 0% in cases of incomplete or no resection (P <0.001). Local recurrence rate was 37.2%. Incomplete gross surgical resection and microscopic infiltration of margins were the most important independent predictors of a poor prognosis. Conclusions The present study confirmed the importance of an aggressive surgical management for retroperitoneal sarcomas to offer these patients the best chance for long-term survival.

RETROPERITONEAL SCHWANNOMAS: DIAGNOSTIC AND THERAPEUTIC IMPLICATIONS

AIMS AND BACKGROUND Schwannomas are a rare group of soft-tissue tumors that are derived from the peripheral nerve sheath and rarely develop in the retroperitoneum. METHODS AND STUDY DESIGN We reviewed the clinicopathological features of 4 patients referred to our unit between October 1999 and March 2004 who on radiological examination were diagnosed with pancreatic, adrenal, psoas and retroperitoneal fat tissue tumors and subsequently underwent surgical treatment. RESULTS The preoperative diagnosis was incorrect in all cases. At time of surgery, we found a mass probably arising from the adrenal gland in 2 patients, a lesion originating from the femoral nerve in 1 patient, and a retroperitoneal mass without a clear site of origin in 1 patient. Pathological evaluation revealed schwannomas in all cases, with no signs of malignancy. Complete surgical excision was performed in all patients without any major postoperative complications. At the time of writing all patients are alive with no evidence of local or distant recurrence. CONCLUSIONS Radical surgical excision is considered the best treatment for these neoplasms, resulting in a very good longterm prognosis.

preoperative Radiotherapy Combined With Intraoperative Radiotherapy Improve Results of Total Mesorectal Excision in Patients With T3 Rectal Cancer

PURPOSE: The survival advantage of preoperative radiotherapy in patients with rectal cancer is still a matter of debate, because its incremental benefit in the total mesorectal excision setting is unclear. This study was designed to evaluate early and long-term results of preoperative radiotherapy plus intraoperative radiotherapy in a homogeneous population of T3 middle and lower rectal cancer patients submitted to total mesorectal excision. METHODS: A series of 113 patients with middle and lower T3 rectal cancer consecutively submitted to total mesorectal excision at a single surgical unit from 1991 to 1997 were divided into two groups according to type of neoadjuvant treatment: preoperative radiotherapy (38 Gy) plus intraoperative radiotherapy (10 Gy; n = 69), and no preoperative treatment (total mesorectal excision; n = 44). Standard statistical analyses were used to evaluate early (downstaging, intraoperative factors, hospital morbidity, and mortality rates) and long-term results (recurrence and survival). RESULTS: Overall, 68.2 percent of patients were downstaged by the preoperative regimens (T0 specimens in 3 cases). Postoperative complications were comparable in the two groups. Five-year, disease-specific survival was 81.4 and 58.1 percent in preoperative radiotherapy plus intraoperative radiotherapy group and total mesorectal excision group, respectively (P = 0.052). Corresponding figures for disease-free survival were 73.1 and 57.2 percent in the two groups, respectively (P = 0.096). The rates of local recurrence at five years were 6.6 and 23.2 percent in preoperative radiotherapy plus intraoperative radiotherapy and total mesorectal excision groups, respectively (P = 0.017). CONCLUSIONS: Preoperative radiotherapy plus intraoperative radiotherapy associated with total mesorectal excision reduce local recurrence rate and improve survival in T3 rectal cancer compared with total mesorectal excision alone.

Four Hundred Consecutive Total Gastrectomies for Gastric Cancer: A Single-Institution Experience

HYPOTHESIS Although total gastrectomy (TG) has been generally accepted as the treatment of choice for upper and middle gastric cancers, some issues are still debated. The objective of this retrospective study was to analyze short- and long-term results of TG (radical and palliative) in a series of 400 patients consecutively admitted to our surgical unit. DESIGN Retrospective cohort study. SETTING Primary and referral hospital care. PATIENTS Hospital records of 400 patients who consecutively underwent TG between January 1981 and June 2005 were reviewed. MAIN OUTCOME MEASURES Surgical complications and survival. RESULTS Three hundred twelve patients underwent radical procedures, and 88 patients underwent palliative procedures. The incidence of postoperative complications was higher among patients who underwent palliative TG (33 of 88 [37.5%]) compared with patients who underwent curative TG (75 of 312 [24.0%]) (P =.01). Mortality was higher among patients who underwent palliative TG (6 of 88 [6.8%]) compared with patients who underwent curative TG (11 of 312 [3.5%]) (P =.18). Five-year survival was 61.8% after curative TG and 12.8% after palliative TG. Ten-year survival was 47.3% after curative TG and 0.0% after palliative TG. CONCLUSIONS This study among 400 consecutive patients who underwent TG at the same surgical unit shows that this surgical procedure in experienced hands can lead to excellent short- and long-term results.

Oxidized Low-Density Lipoprotein Biomarkers in Patients with End-Stage Renal Failure: Acute Effects of Hemodialysis

Objective: To assess the effect of end-stage renal failure on oxidized low-density lipoprotein (OxLDL) biomarkers and the acute effects of hemodialysis. Oxidized phospholipids (OxPL) on apolipoprotein B-100 (apoB) particles (OxPL/apoB) have been associated with cardiovascular disease and new cardiovascular events. Patients with end-stage renal failure have increased oxidative stress and are at significantly increased risk of cardiovascular disease. Methods and Results: Fifty-two stable patients with end-stage renal failure undergoing chronic hemodialysis were included in the study. Pre and post hemodialysis blood samples were obtained for measurement of OxLDL biomarkers: oxidized phospholipids (OxPL) on apolipoprotein B-100 (apoB) particles (OxPL/apoB) measured by antibody E06, IgG and IgM autoantibody titers to copper-oxidized LDL (Cu-OxLDL) and malondialdehyde (MDA)-LDL, IgG and IgM apolipoprotein B-100-immune complexes (IC/apoB). Traditional laboratory variables as well as C-reactive protein (CRP) and lipoprotein(a) [Lp(a)] were also measured. For the baseline variables, the distribution of OxPL/apoB and Lp(a) were skewed to lower values, and a strong correlation was noted between OxPL/apoB and Lp(a) (r = 0.94, p < 0.0001). No major associations were noted between OxLDL biomarkers and age, gender or dialytic age. There were also no correlations between OxLDL biomarkers and traditional risk factors, CRP, body mass index, serum creatinine, hypertension or intravenous iron therapy. Following dialysis, there as a significant reduction in OxPL/apoB (–7.5%, p = 0.048) and triglyceride levels (–10.8%, p = 0.005). All other OxLDL biomarkers, CRP, total cholesterol, LDL-C, HDL-C and apoB-100 increased significantly (range 6.3–26.9%, p value range 0.005 to <0.0001). Total protein plasma levels increased 8.8% (p = 0.014 compared to predialysis) following dialysis, consistent with a hemoconcentration effect of hemodialysis. Conclusion: In end-stage renal failure patients undergoing hemodialysis, a reduction in OxPL/apoB levels was noted, despite the hemoconcentrating and strong pro-oxidant milieu of hemodialysis. Studies in larger populations of end-stage renal failure patients are needed to assess whether these findings predict future clinical outcomes.

Does Nutrition Support Stimulate Tumor Growth in Humans

Many studies have been conducted to ascertain if nutrition support (NS), either as parenteral nutrition (PN) or enteral nutrition (EN), stimulates tumor growth and causes cancer progression, but after almost 30 years, the question remains at least in part unresolved. In this study, previous studies were reviewed to evaluate the effect of NS on tumor growth, tumor proliferation, tumor apoptosis, and cancer-related survival in humans. MEDLINE and PubMed were searched using combinations of the following keywords: PN, EN, tumor growth, tumor proliferation, tumor apoptosis, arginine, ω-3 fatty acids, and glutamine. Unfortunately, the effect of nutrition support on tumor growth has been assessed only in terms of tumor proliferation, whereas the interferences on tumor apoptosis have never been determined. Overall, the results seem conflicting and inconclusive. Similarly, it remains unknown if PN or EN enriched with specific nutrients such as arginine, ω-3 fatty acids, and glutamine can affect tumor growth in humans. It is hoped that further studies will elucidate if NS with conventional or specific nutrients stimulates tumor proliferation, interferes with tumor apoptosis, and causes cancer progression.

Chilaiditi's syndrome.

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